I . DNA & RNA | 4. The role of genetic variations in the pathogenesis of diseases; methods to study genetic factors Flashcards
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
1. What is the difference between the genomes of two unrelated people?
The difference between the genomes of two unrelated people is around 0,1% - max 0,5% (3 million base pairs), meaning your genome is almost 99,5% similar to any other person.
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
2. What is the consequence of genetic variations?
The consequence of these variations are the phenotype (height, hair color, skin color, etc.), diseases, risk factor for illnesses and many other things => monogenic disorder
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
3. What is monogenic disorder caused by?
Monogenic disorder are caused by a variation in a single gene (sickle cell anemia, cystic fibrosis, Huntington disease)
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
4. What are the causes of differences between individuals ?
Causes of differences between individuals include independent assortment, the exchange of genes (crossing over and recombination) during meiosis and various mutational events.
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
5. What are the definition and features of BASE CHANGE?
Base change: modification of a single nucleotide (can be insertion/deletion, but usually a substitution)
- Responsible for 0,1/0,5% of the difference between two unrelated individuals => affects alleles
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
6. What are the definition and features of LENGTH CHANGE?
Length variation: a change in more than one nucleotide
- There can be 0 copies or several hundred of them
- 0,4/0,5% if the difference between two unrelated individuals => affects alleles
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
7. What is SNP (polymorphism)?
SNP (polymorphism) = single base change occurs in a population at a frequency of 1% or higher
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
8. What is Point mutation?
single base change occurs in less than 1% of a population
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
9A. What are Length variations that are polymorphisms?
- Microsatellites
- Variable number of tandem repeats (minisatellites)
- Copy number variations (CNV)
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES - Length variations that are polymorphisms
9B. What are Microsatellites?
The length of the repeated block is between 2-10 bp long
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES - Length variations that are polymorphisms
9B. What are Variable number of tandem
repeats (minisatellites)?
length of the repeated block is between 10- 100/1000 bp long
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES - Length variations that are polymorphisms
9C. What are Copy number variations (CNV)?
length of the repeated block is extremely long; 10,000 – 100,000 bp
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
10A. What is the difference between mutation and polymorphism?
Mutation usually results in diseases, while polymorphisms (SNP for example) either increase or decrease the risk of a certain disease.
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
10B. Mutation usually results in diseases, while polymorphisms (SNP for example) either increase or decrease the risk of a certain disease.
=> Give an example?
Ccystic fibrosis is the result of a mutation in a single gene for the CFTR protein, which normally acts as a channel that allows cells to release chloride and other ions, but when defective (as in CF), it results in impaired salt balance and production of thick mucus (no water transported).
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
11. What are Possible effects of SNPs and point mutations (in coding regions)?
- Nothing (biological effect mRNA stability)
- False splicing (introns cutting)
- Change of one amino acid
- Nonsense mutation (premature stop)
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
12. What are Possible effects of insertions or deletions (in coding regions):
Frame-shift mutation
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
13. What are Possible effects of length variations (in coding regions)?
- 3n bps: n amino acids
- 3n+1, or 3n+1 bps: frame-shift mutation
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
14. What are Possible effects of genetic variations in non-coding regions?
Alternation of the binding affinity of transcription factors, micro-RNA molecules etc.
I. ROLE OF GENETIC VARIATIONS IN PATHOGENESIS OF DISEASES
15. Describe Etiology of disease
- 100% heritability: completely due to genetic factors (monogenic disorders)
- 0% heritability: completely due to environmental factors (but no such thing really exists)
- Complex diseases: many gene variations and environmental factors both contribute to the disease (malignant tumors, diabetes, cardiovascular diseases)
II. METHODS TO STUDY GENETIC FACTORS
1. What are the 4 methods to study genetic factors?
- Candidate gene analysis
- GWAS (genome wide association study)
- Case-control study
- Transmission disequilibrium test
II. METHODS TO STUDY GENETIC FACTORS
2. What are the features of candidate gene analysis?
- One commonly used technique to identify genetic risk factors for complex disorders such as alcoholism is the candidate gene approach, which directly tests the effects of genetic variants of a potentially contributing gene in an association study.
- A hypothesis is set up surrounding selected genes
- Specific targets are analyzed
- Sometimes, important target may be omitted
II. METHODS TO STUDY GENETIC FACTORS
3. What is GWAS (genome wide association study)?
- Genome-wide association studies (GWAS) help scientists identify genes associated with a particular disease (or another trait).
- This method studies the entire set of DNA (the genome) of a large group of people, searching for small variations, called single nucleotide polymorphisms or SNPs (pronounced “snips”).
- Polymorphisms everywhere in the genome/whole genome
- No hypothesis => just investigate everything and look for
some connection - Statistical analysis provides correction for multiple testing
II. METHODS TO STUDY GENETIC FACTORS
3. What is Case-control study?
- Allele or genotype frequencies of two groups (case and control) are compared to see if statistically significant differences can be observed
II. METHODS TO STUDY GENETIC FACTORS
4. What is Transmission disequilibrium test?
- Affected/ill children are studied to see which allele they get from each parent => only heterozygote parents can be included in the study
- If there is a monogenic disorder => all the children studied will be affected and in 100% of them, they will have gotten the gene from either their mother or father
